A liposome is a closed vesicle having a lipid bimolecular membrane formed mainly of a phospholipid. Since a liposome has a similar structure and a similar function as a cell membrane, It will not stimulate easily an immunity system (low antigen) and it has a high safety level as a material. Moreover, it can retain a water-soluble medicine in an internal aqueous phase which is surrounded by a lipid bimolecular membrane, and it can retain a lipo-soluble medicine inside of the lipid bimolecular membrane. Therefore, it is possible to stably encapsulate medicinal properties which are originally easily deactivated. Active research and development have been made for application of a liposome in the field of pharmaceutical products, foods and cosmetics. In particular, it has been widely studied a medicine encapsulated liposome which is effectively applicable to a drug delivery system (DDS) (the content of studies are such as an adjustment of a particle size or a property of a lipid membrane of a liposome, and a targeting property to a specific cell) and a preparation method of a medicine encapsulated liposome.
In the present invention, the number of the lipid bimolecular membrane for constituting one liposome may be one, and it may be plural. That is, when the number of lipid bimolecular membrane is one, the bimolecular membrane concerned constitutes the outer shell of a liposome. On the other hand, when one liposome is composed of two or more lipid bimolecular membranes, any one of two or more lipid bimolecular membrane will constitute the outer shell of the liposome, and the remaining lipid bimolecular membranes will exist in the inside of the lipid bimolecular membrane which constitutes the outer shell.
The conventional liposome is manufactured by the way of forming lipid bimolecular membrane in one step, therefore, it is common that both inside and outside membrane of the liposome are made of the same constituting component (for example, refer to Patent document 1). Moreover, since the chemical property of the outer membrane participates in the dynamic state of the liposome in the living body, it may be employed a method to modify the outer membrane after usual preparation of the liposome. For example, in order to increase water solubility, a method may be employed in which the lipid of the outer membrane is combined with a polyoxyalkylene group (for example, refer to Non-patent document 1).
There has not been proposed a technique aiming at an improvement of a behavior in a living body such as an increased ratio of the encapsulated medicine or a controlled release (sustained-release) by making the constituting component of the inner membrane of the liposome which contacts with the medicine which should be sent different from an embodiment of the outer membrane. Or there has not been proposed a manufacturing method of a liposome having a different constituting component of an inner and an outer membrane.
Patent Document 1: Japanese Patent Application Publication open to public inspection (JP-A) 2005-162678
Non-patent Document 1: Biophys. J. 35,637-652, 1981